This research is designed to study the role of granulocytes in the etiology of increased permeability edema resulting from altered microvascular endothelial integrity in the sheep lung. It plans to clarify the etiology of microembolic lung injuries by depleting circulating granulocytes in the chronically instrumented, unanesthetized sheep with lung lymph fistulas, determine whether diverse lung injuries are qualitatively similar and if granulocytes are the final common pathway in the lungs' response to injury, and clarify the role of complement and lysosomal enzymes in these lung injuries. Healthy female feeder lambs undergo a left thoracotomy during which cannulas are implanted in the pulmonary artery and left atrium. A band containing an ultrasonic flow meter probe is placed around the orgin of the main pulmonary artery (for later determination of cardiac output). The sheep is allowed to recover. A second operative procedure is performed, identifying and dividing the caudal mediastinal lymph node through a right thoracotomy and the efferent lymph duct from this node is cannulated, allowing for the collection of pure lung lymph. The sheep is allowed to recover and experiments are performed on the awake, unanesthetized animal. Baseline hemodynamic and lung lymph fluid and protein flux data are collected during a stable control period and after microemboli, (air emboli) injection into the lung. Circulating white blood cells are then depleted with intra-arterial injection of nitrogen mustard. Baseline and post-embolic data are again collected. Experiments are repeated in the normal and granulocytopenic sheep with E. coli endotoxin and Pseudomonas bacteremia as the injury agents, and with activated complement infusions. A pilot study in the anesthetized sheep has suggested granulocytes are necessary for the increased permeability edema resulting from altered microvascular endothelial integrity after microemboli. These experiments will extend this obsveration to the chronic, unanesthetized sheep and to lung injuries of diverse nature.